This component addresses these parts of our unifying thesis: "Altering central serotonin metabolism, or revising environmental contingencies for behavior, may reduce the substance involvement and antisocial behavior of these persons. However, the genetically determined disposition will remain, and such treatments must continue indefinitely to have sustained effects." Treatment studies must begin with small-scale feasibility trials later progressing to larger, hypothesis-testing trials. Because so few treatment studies specifically have addressed antisocial drug dependence (Drug-Dependence combined with either Conduct Disorder or Antisocial Personality Disorder), this component will be an "incubator" for small- scale early treatment trials for the condition. The resulting preliminary data will guide the design of larger studies to be supported under new grant applications. We first will conduct three feasibility studies in Years 01-02. (a) Project 1 explores the feasibility of fluoxetine trials for the common adolescent triad of drugs dependence, conduct disorder, and depression. Fluoxetine is a selective serontonin reuptake inhibitor, and those three conditions all may have underlying central serotonin abnormalities. (b)Project 2 explores the feasibility of treating antisocial drug dependence in adults by revising environmental contingencies for drug use. It will use court sanctions or welfare benefits, contingencies native to these patients' environments. If successful, it may lead to sustainable, long-term treatments in these difficult patients. (c ) Project 3 examines the feasibility of contingent reinforcement to secure family participation in the treatment of youths with antisocial drug dependence. Adolescent patients' parents, often themselves antisocial and substance- involved, frequently fail to support therapeutic goals for the adolescents. This project attempts to secure parental support for the juvenile's abstinence and prosocial behavior by reinforcing both parent and child for the child's progress. Specific aims for subsequent years are: (d) to submit to NIDA during Years 02 or 03 at least one R01 grant application based on the above three trials. (e) Based on those outcomes and new findings in the literature, to select and complete four more early treatment trials during Years 03-05. (f) Those early treatment trials should lead to one or two more R01 applications, or to a new, larger-scale treatment component for the year 06-10 renewal application for this center.